With the goal to facilitate the global multi-method analysis (GMMA) of biophysical protein interactions data, we have further expanded the software SEDPHAT with new simulation and analysis models. This platform offers a seamless combination of data types from different techniques, with a variety of interaction models, and specific statistical functions for the analysis of multi-component interactions in a multi-method approach. Specifically, in the reporting period we have expanded the capabilities of the software for isothermal titration calorimetry (ITC). We have shown that the classical c-value criterion for useful sample concentrations in ITC becomes meaningless in the context of multi-site and multi-component interactions. Therefore, we have developed a new experimental planning tool that is based on the visualization of differential enthalpy isotherms. Two-dimensional or three-dimensional depictions of these enthalpy changes with sample concentration in two or three components, respectively, allow the user to identify promising experimental conditions and simulate ITC data. These may be combined in a global analysis to explore whether experiments will likely generate information to determine thermodynamic binding parameters. We believe this will be very helpful in the study of multi-protein and multi-site interactions by ITC. In order to disseminate this tool and facilitate its application by colleagues, we have held multiple workshops at NIH in Bethesda, which have generated positive feedback and software improvements. This was accompanied by the release of a modified version of our SEDPHAT software, called ITCsy, that streamlines applications to ITC.